In the Journals

Cocoa may improve walking ability in patients with PAD

Mary M. McDermott

Daily consumption of cocoa with epicatechin improved 6-minute walk distance, blood flow to the legs and skeletal muscle health in patients with peripheral artery disease, according to a study published in Circulation Research.

In this phase 2 randomized clinical trial, patients with PAD who ingested a cocoa beverage containing 15 g cocoa and 75 mg epicatechin daily improved 6-minute walk distance at 6-month follow-up by 42.6 m (P = .005) at 2.5 hours after consuming a final portion at the end of the 6-month study, compared with participants who ingested a placebo beverage.

“Patients with PAD have significantly impaired walking ability and few therapies have been identified that improve walking performance,” Mary M. McDermott, MD, Jeremiah Stamler professor, professor of general internal medicine and geriatrics and professor of preventive medicine at Northwestern University Feinberg School of Medicine, told Healio. “Cocoa is accessible, relatively affordable and has minimal side effects. If these findings are confirmed, the results may have important implications for improving mobility in people with PAD.”

Moreover, calf muscle biopsies revealed that cocoa intake improved mitochondrial activity (P = .013), increased capillary density (P = .014), improved calf muscle perfusion (P = .098) and reduced central nuclei (P = .024), compared with placebo. A one-sided P-value of less than .1 was considered statistically significant.

“The findings were consistent with our hypotheses,” McDermott said in an interview. “The magnitude of improvement in 6-minute walk distance was larger than might have been anticipated. It was of particular interest that there were simultaneous improvements in some measures of skeletal muscle health, measured by calf muscle biopsy, and in blood flow to the legs, measured by MRI.”

In other findings, at 6 months, the cocoa group improved 6-minute walk distance by 18 m (P = .12) when measured 24 hours after a study beverage compared with the placebo group.

For this study, researchers randomly assigned 44 patients with PAD (mean age, 72 years; mean ankle-brachial index, 0.66) to consume a daily cocoa or placebo beverage with the aim determining whether 6-months of intake improved walking performance. Of the cohort, 91% completed follow up.

Potential benefit from dark chocolate

“Not all chocolate is the same. We studied dark chocolate, which was high in cocoa flavanols,” McDermott told Healio. “Cocoa that is alkalized would not be expected to have the same effect. So dark chocolate that is not alkalized may have benefits. However, our trial was a pilot study with a small sample size and further study is needed to reach a definitive conclusion about benefits of cocoa.”

For future research, “The investigative team has applied for additional funding for a larger and definitive study of the effects of cocoa on walking ability in people with PAD,” McDermott said in an interview.

‘Compelling preliminary evidence’

“In the calf muscle biopsies of the patients with PAD, there was a relative increase of mitochondrial cytochrome c [oxidase] activity in the cocoa group that was largely produced by a decline in the placebo group,” Reiko Matsui, MD, assistant professor at Boston University School of Medicine, and Naomi M. Hamburg, MD, of the Whitaker Cardiovascular Institute at Boston University School of Medicine, wrote in a related editorial. “This finding suggests that cocoa may protect the muscle from deterioration in mitochondrial respiratory capacity. There was no evidence of differences in either [peroxisome proliferator-activated receptor-gamma coactivator 1-alpha] or citrate synthase activity, suggesting that the effect on mitochondrial function may not have been mediated by a change in mitochondrial biogenesis.

“Taken together, the pilot study by McDermott and colleagues provides compelling preliminary evidence to support a potential benefit of epicatechin-rich cocoa on walking ability along with protection from worsening of calf muscle perfusion, skeletal muscle injury and mitochondrial dysfunction,” Matsui and Hamburg wrote. “Additional clinical studies are warranted to evaluate the clinical efficacy of cocoa and other polyphenol-based therapies in patients with PAD. Someday, we may be able to prescribe eating more chocolate to our patients with PAD.” – by Scott Buzby

Disclosures: McDermott reports she received other research support from ArtAssist, Chromadex, Helixmith and Reserveage. One author reports he is co-founder and stockholder of Cardero Therapeutics. Hamburg reports she is a consultant for Bayer, Merck and Sanifit and has equity interest in Acceleron Pharma. The other authors and Matsui report no relevant financial disclosures. Hershey provided the intervention and placebo beverages for the trial. Mars analyzed the blood samples for presence of metabolites of cocoa in the two groups.

Mary M. McDermott

Daily consumption of cocoa with epicatechin improved 6-minute walk distance, blood flow to the legs and skeletal muscle health in patients with peripheral artery disease, according to a study published in Circulation Research.

In this phase 2 randomized clinical trial, patients with PAD who ingested a cocoa beverage containing 15 g cocoa and 75 mg epicatechin daily improved 6-minute walk distance at 6-month follow-up by 42.6 m (P = .005) at 2.5 hours after consuming a final portion at the end of the 6-month study, compared with participants who ingested a placebo beverage.

“Patients with PAD have significantly impaired walking ability and few therapies have been identified that improve walking performance,” Mary M. McDermott, MD, Jeremiah Stamler professor, professor of general internal medicine and geriatrics and professor of preventive medicine at Northwestern University Feinberg School of Medicine, told Healio. “Cocoa is accessible, relatively affordable and has minimal side effects. If these findings are confirmed, the results may have important implications for improving mobility in people with PAD.”

Moreover, calf muscle biopsies revealed that cocoa intake improved mitochondrial activity (P = .013), increased capillary density (P = .014), improved calf muscle perfusion (P = .098) and reduced central nuclei (P = .024), compared with placebo. A one-sided P-value of less than .1 was considered statistically significant.

“The findings were consistent with our hypotheses,” McDermott said in an interview. “The magnitude of improvement in 6-minute walk distance was larger than might have been anticipated. It was of particular interest that there were simultaneous improvements in some measures of skeletal muscle health, measured by calf muscle biopsy, and in blood flow to the legs, measured by MRI.”

In other findings, at 6 months, the cocoa group improved 6-minute walk distance by 18 m (P = .12) when measured 24 hours after a study beverage compared with the placebo group.

For this study, researchers randomly assigned 44 patients with PAD (mean age, 72 years; mean ankle-brachial index, 0.66) to consume a daily cocoa or placebo beverage with the aim determining whether 6-months of intake improved walking performance. Of the cohort, 91% completed follow up.

Potential benefit from dark chocolate

“Not all chocolate is the same. We studied dark chocolate, which was high in cocoa flavanols,” McDermott told Healio. “Cocoa that is alkalized would not be expected to have the same effect. So dark chocolate that is not alkalized may have benefits. However, our trial was a pilot study with a small sample size and further study is needed to reach a definitive conclusion about benefits of cocoa.”

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For future research, “The investigative team has applied for additional funding for a larger and definitive study of the effects of cocoa on walking ability in people with PAD,” McDermott said in an interview.

‘Compelling preliminary evidence’

“In the calf muscle biopsies of the patients with PAD, there was a relative increase of mitochondrial cytochrome c [oxidase] activity in the cocoa group that was largely produced by a decline in the placebo group,” Reiko Matsui, MD, assistant professor at Boston University School of Medicine, and Naomi M. Hamburg, MD, of the Whitaker Cardiovascular Institute at Boston University School of Medicine, wrote in a related editorial. “This finding suggests that cocoa may protect the muscle from deterioration in mitochondrial respiratory capacity. There was no evidence of differences in either [peroxisome proliferator-activated receptor-gamma coactivator 1-alpha] or citrate synthase activity, suggesting that the effect on mitochondrial function may not have been mediated by a change in mitochondrial biogenesis.

“Taken together, the pilot study by McDermott and colleagues provides compelling preliminary evidence to support a potential benefit of epicatechin-rich cocoa on walking ability along with protection from worsening of calf muscle perfusion, skeletal muscle injury and mitochondrial dysfunction,” Matsui and Hamburg wrote. “Additional clinical studies are warranted to evaluate the clinical efficacy of cocoa and other polyphenol-based therapies in patients with PAD. Someday, we may be able to prescribe eating more chocolate to our patients with PAD.” – by Scott Buzby

Disclosures: McDermott reports she received other research support from ArtAssist, Chromadex, Helixmith and Reserveage. One author reports he is co-founder and stockholder of Cardero Therapeutics. Hamburg reports she is a consultant for Bayer, Merck and Sanifit and has equity interest in Acceleron Pharma. The other authors and Matsui report no relevant financial disclosures. Hershey provided the intervention and placebo beverages for the trial. Mars analyzed the blood samples for presence of metabolites of cocoa in the two groups.